bims-mitrat 2026-10-04 papers

bioRxiv. 2026 Sep 22. pii: 2026.09.21.753229. [Epub ahead of print]

Exogenous L6 myotube mitochondrial transplantation attenuates hypertrophy and elicits a unique proteomic signature in phenylephrine-treated H9C2 cardiomyocytes.

Nicholas J Kontos, George J Kontos, Dustyn T Lewis, Samuel C Norton, Bradley A Ruple, Andreas N Kavazis, Darren T Beck, Melissa D Boersma, Christopher B Mobley, Danielle J McCullough, Ahmed Ismaeel, Michael D Roberts.

Mitochondrial transplantation has recently emerged as an alternative treatment for cardiovascular disease (CVD), aimed at increasing mitochondrial number and improving mitochondrial function. Though mitochondrial dysfunction is a key factor in the development of right ventricular hypertrophy/failure, the effects of mitochondrial transplantation on disease mitigation have been largely unexplored. Therefore, this in vitro study aimed to determine whether the transplantation of exogenous L6 myotube mitochondria mitigates negative outcomes in H9C2 cardiomyocytes that were stimulated to hypertrophy with phenylephrine. Control (CTL), control with mitochondrial transplantation (MitoTx), Phenylephrine only (Phe-only), and phenylephrine with mitochondrial transplantation (Phe+MitoTx) treatments were evaluated. Pilot experiments indicated mitochondrial transplantation into healthy cardiomyocytes acutely increased Complex I-linked oxidative phosphorylation (OXPHOS) capacity (p=0.005) and maximal respiratory capacity (p=0.022) within 24 hours, and these data alongside microscopic evidence of fluorescently labeled L6 mitochondria in H9C2 cardiomyocytes suggested successful transplantation. Regarding treatment comparisons, Phe-only showed a significant increase in cell area (p<0.05), while Phe+MitoTx blunted the hypertrophic cardiomyocyte response. Consistent with these results, proteomic analysis of 4,806 proteins showed that transplantation enriched the mitochondrial proteome, impacting pathways including OXPHOS, respiration, fatty acid and amino acid metabolism, while suppressing extracellular matrix remodeling and de-differentiation signatures. This response was observed in healthy and phenylephrine-stressed cardiomyocytes. In conclusion, our in vitro data indicates that transplantation of L6 skeletal muscle mitochondria mitigates negative effects induced by phenylephrine in H9C2 cardiomyocytes. However, more rigorous in vivo studies are needed to determine if this is a suitable approach for disease mitigation.

DOI: https://doi.org/10.64898/2026.09.21.753229

Adv Sci (Weinh). 2026 Sep 27. e77713

Mitochondria-Targeted Nanotherapeutics: A Promising Strategy in Modulating Mitochondrial Function, Transfer, and Transplantation.

Yuanyuan Su, Zhiyan Gong, Jiao Mu, Lili Huang, Pengfei Yang, Chenli Zhang, Lingshan Zhao, Liling Yang, Jun Deng, Xiaohui Liao.

Mitochondria, as organelles with a critical role in maintaining cellular activities, are also vulnerable to dysfunction, which contributes substantially to the pathogenesis of various systemic diseases. Nanomaterials, owing to their tunable physicochemical properties and precise bio-interfacial capabilities, offer innovative platforms not only for delivering general mitochondria-targeted therapy but also for enabling-with promising potential-the emerging paradigms of mitochondrial transfer and transplantation. Nevertheless, a dedicated review systematically summarizing progress in this specific subfield is lacking. To fill this knowledge gap, this review provides a structured synthesis that spans from the biological basis of mitochondrial function and transfer to the broad applications of nanomaterials in mitochondria-targeted therapies, with a dedicated analysis of their roles in mitochondrial targeting, functional modulation, and gene editing. A key topic of this review is the emerging role of nanomaterials in assisting mitochondrial transplantation and transfer. By integrating these insights, this work bridges nanotechnology and mitochondrial medicine, offering a valuable resource for developing organelle-specific therapeutics.

Keywords: mitochondria; mitochondrial transfer; mitochondrial transplantation; nanomaterials; nanotherapeutics

DOI: https://doi.org/10.1002/advs.77713

Front Cell Dev Biol. 2026 ;14 1943282

Mitochondrial pearling: membrane biophysics, Ca2+-dependent regulation, mtDNA nucleoid dynamics, and emerging links to mitochondrial quality control and neurological disorders.

Ye Chen, Fajuan Tang, Xihong Li.

Mitochondrial dynamics has long been interpreted primarily through fission and fusion, yet tubular mitochondria can also undergo rapid pearling, a phenomenon in which elongated mitochondria reorganize into a beads-on-a-string morphology while retaining a continuous imaged contour. The occurrence and biological relevance of mitochondrial pearling require careful study. The dimensionless tension-bending ratio used to organize these observations is a heuristic analogy to single-membrane tubes, not a validated quantitative model of the mitochondrial double membrane. Evidence does not yet establish a continuous sequence from pearling through coordinated outer- and inner-membrane scission to mitophagy or intercellular mitochondrial transfer; those links are therefore presented as hypotheses and testable predictions. We use the provisional term "candidate disease-associated sustained pearling phenotype" only for within-study events that meet dynamic pearling criteria and show longer duration or delayed/failed reversal relative to appropriately matched controls. No universal duration threshold or validated pearling-defined disease entity currently exists. Event duration, wavelength, un-pearling kinetics, separate outer- and inner-membrane continuity, and the fate of individual pearls should be measured together to determine whether sustained events are incidental, adaptive, or causally involved in disease.

Keywords: Ca2+; mitochondrial pearling; mitochondrial transfer; mitophagy; mtDNA nucleoid; neurological disease; sustained pearling phenotype

DOI: https://doi.org/10.3389/fcell.2026.1943282

Cardiovasc Toxicol. 2026 09 30. pii: 121. [Epub ahead of print]26(10):

Intravenous Mitochondrial Injection Attenuates Methanol-Induced Cardiotoxicity Through Restoration of Mitochondrial Function and Suppression of Oxidative Stress.

Ahmad Salimi, Hanieh Delavari, Hamed Karroubian, Behrooz Elyasi, Mina Dehghanypoor, Elahe Zeynali, Salva Zaki, Zhaleh Jamali.

Methanol poisoning induces severe mitochondrial dysfunction through inhibition of mitochondrial respiration, excessive reactive oxygen species (ROS) generation and oxidative stress. The present study investigated whether injection of freshly isolated mitochondria, could attenuate methanol-induced cardiac mitochondrial dysfunction and oxidative damage in rat. Adult male Wistar rats were randomly allocated into five experimental groups: control, methanol, methanol plus single mitochondrial injection, methanol plus repeated mitochondrial injection (double) and mitochondria alone. Fresh functional mitochondria were isolated from healthy donor cardiac tissue and administered intravenously (250 µg/kg), 30 min after methanol intoxication. Serum cardiac injury biomarkers, including creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), were measured. Oxidative stress was evaluated by determining malondialdehyde (MDA) and glutathione (GSH) levels. Cardiac mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial ROS production, and mitochondrial membrane potential (MMP). Methanol intoxication significantly increased serum cardiac injury biomarkers, ROS generation, lipid peroxidation, and mitochondrial swelling while markedly reducing GSH content, SDH activity, and MMP compared with the control group. Mitochondrial injection significantly attenuated oxidative stress, decreased ROS production, restored antioxidant capacity, improved SDH activity, reduced mitochondrial swelling, and preserved MMP. Repeated mitochondrial administration showed relatively greater improvement than single administration, although no consistent dose-response relationship was observed. Also, histopathological examinations demonstrated significant recovery following mitochondrial injection. Fresh mitochondrial injection effectively ameliorated methanol-induced cardiotoxicity by reducing oxidative stress, preserving mitochondrial integrity, and restoring mitochondrial function in cardiac tissue. These findings suggest that mitochondrial injection represents a promising mitochondria-targeted therapeutic approach for methanol-induced cardiotoxicity.

Keywords: Alcohol poisoning; Cardiotoxicity; Methanol toxicity; Mitochondrial transplantation; Oxidative stress

DOI: https://doi.org/10.1007/s12012-026-10199-4